Fully automatic, semiautomatic, and manual corneal nerve fiber analysis in patients with sarcoidosis

Purpose: No guidelines are available on the preferred method for analyzing corneal confocal microscopy (CCM) data. Manual, semiautomatic, and automatic analyzes are all currently in use. The purpose of the present study was threefold. First, we aimed to investigate the different methods for CCM analysis in patients with and without small fiber neuropathy (SFN). Second, to determine the correlation of different methods for measuring corneal nerve fiber length (CNFL) and nerve fiber area (NFA). Finally, we investigated the added value of automatic NFA analysis.Methods: We included 20 healthy controls and 80 patients with sarcoidosis, 31 with established SFN and 49 without SFN. The CNFL was measured using CCMetrics, ACCMetrics, and NeuronJ. NFA was measured with NFA FIJI and ACCMetrics NFA.Results: CNFL and NFA could not distinguish sarcoidosis with and without SFN or healthy controls. CCMetrics, NeuronJ, and ACCMetrics CNFL highly correlated. Also, NFA FIJI and ACCMetrics NFA highly correlated. Reproducing a nonlinear formula between CNFL and NFA confirmed the quadratic relation between NFA FIJI and ACCMetrics CNFL. CCMetrics and NeuronJ instead showed a square root relationship and seem to be less comparable owing to differences between automatic and manual techniques.Conclusions: ACCMetrics can be used for fully automatic analysis of CCM images to optimize efficiency. However, CNFL and NFA do not seem to have a discriminatory value for SFN in sarcoidosis. Further research is needed to determine the added value and normative values of NFA in CCM analysis.Translational Relevance: Our study improves the knowledge about CCM software and pathophysiology of SFN.Neurological Motor Disorder

New phenotyping questionnaire for diagnosing sarcoidosis-associated small fiber neuropathy

Small fiber neuropathy is a common complication in patients with sarcoidosis and its prevalence is estimated at 40–86%. The underlying mechanism influences the presentation of small fiber neuropathy. For example, patients with metabolic diseases are often associated with a classic length-dependent small fiber neuropathy pattern, while patients with inflammatory diseases are more often present with a non-length-dependent small fiber neuropathy. Detailed phenotyping may be useful to improve diagnostic efficiency, as a clue to underlying mechanisms and as a precondition for personalized medicine. This study examined four phenotypes distinguishing between length-dependent and non-length-dependent presentation with a new subdivision for continuous and intermittent presentation. Forty-eight sarcoid patients with symptoms and at least two clinical signs of small fiber neuropathy and normal nerve conduction studies were classified as having probable small fiber neuropathy. A new small fiber neuropathy phenotyping questionnaire has been developed that allows patients to mark the anatomical locations of pain at three different levels: the skin, muscles, and joints. The location of symptoms was used to define length dependence, and two colors were used to distinguish continuous (red) from intermittent (blue) symptoms. In addition, skin biopsy, corneal confocal microscopy, Sudoscan and water immersion skin wrinkling were used to investigate a correlation between the four phenotypes, sensory function, nerve fiber density, and autonomic nerve function. Overall, 35% of patients with probable small fiber neuropathy showed length-dependent symptoms and 44% showed non-length-dependent symptoms while 21% suffered from non-neuropathic musculoskeletal pain. The distinction between intermittent and continuous symptoms showed significantly less continuous than intermittent non-length-dependent symptoms (odds ratio = 0.3, P = 0.01). Moreover, continuous length-dependent symptoms were the only phenotype that correlated with thermal threshold testing (R = 0.3; P = 0.02) and the small fiber neuropathy screening list (R = 0.3; P = 0.03). In addition, thermal threshold testing (TTT) also correlated with the small fiber neuropathy (SFN) screening list (R = 0.3; P = 0.03). Other diagnostic methods showed no correlation with any of the four defined phenotypes. A novel finding is that TTT is only associated with continuous length-dependent pain, suggesting that TTT could result in more false negatives in patients with other pain phenotypes. Determining the pathophysiologic mechanisms could help develop new diagnostic methods. If patients suspected of SFN show symptoms without a length-dependent continuous presentation, the diagnosis should focus less on the diagnostic methods used. Neurological Motor Disorder

In Reply: Decompressive Surgery for Diabetic Neuropathy: Waiting for Incontrovertible Proof

Neurological Motor Disorder

The Tinel sign has no diagnostic value for nerve entrapment or neuropathy in the legs

Neurological Motor Disorder

Outcome of Carpal Tunnel Release and the Relation With Depression

Development and application of statistical models for medical scientific researc

Can novel non-invasive autonomic tests help discriminate between pure autonomic failure and multiple system atrophy?

Background: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are rare disorders causing severe autonomic failure. Their initially similar clinical presentation may lead to years of diagnostic difficulties. Improving the differentiation would have an important impact on patients and families in view of better prediction of disease progression. Objective: To investigate whether several new non-invasive autonomic tests are beneficial in discriminating between PAF and MSA. Methods: Patients and controls underwent two tests examining the autonomic innervation of the skin (Sudoscan and water-induced skin wrinkling) and one test measuring retinal nerve fiber layer thickness in the eye. Results: The skin vasomotor tests yielded differences between the disease and control groups, but did not discriminate between PAF and MSA. No differences in retinal nerve fiber layer thickness were found between the groups. Conclusion: The tests applied in this study may help to confirm autonomic failure but did not support the differential diagnosis between PAF and MSA.Neurological Motor Disorder

Component-resolved diagnosis and beyond: Multivariable regression models to predict severity of hazelnut allergy

Background: Component-resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity. Aim: To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy. Methods: Patients reporting hazelnut allergy (n = 423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during Double-blind placebo-controlled food challenge [DBPCFC]) were categorized in mild, moderate, and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD- and extract-based). Odds ratios (ORs) and areas under receiver-operating characteristic (ROC) curves (AUCs) were used to evaluate their predictive value. Results: Cor a 9 and 14 were positively (OR 10.5 and 10.1, respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70-073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk) increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3%, and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker. Conclusion: A model combining CRD with clinical background and extract-based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd